Immunotoxicity of engineered nanomaterials and their role in asthma.

The toxicity of engineered nanomaterials (ENMs) in vivo and in vitro has formed the basis of most studies. However, the toxicity of ENMs, particularly on the immune system, i.e. immunotoxicity, and their role in manipulating it, are less known. This review addresses the initiation or exacerbation as well as the attenuation of allergic asthma by a variety of ENMs and how they may be used in drug delivery to enhance the treatment of asthma. This review also highlights a few research gaps in the study of the immunotoxicity of ENMs, for example, the potential drawbacks of assays used in immunotoxicity assays; the potential role of hormesis during dosing of ENMs; and the variables that result in discrepancies among different studies, such as the physicochemical properties of ENMs, differences in asthmatic animal models, and different routes of administration.

Dissolution and biodurability: Important parameters needed for risk assessment of nanomaterials.

Biopersistence and biodurability have the potential to influence the long-term toxicity and hence pathogenicity of particles that deposit in the body. Therefore, biopersistence and biodurability are considered to be important parameters needed for the risk assessment of particles and fibres. Dissolution, as a measure of biodurability, is dependent on the chemical and physical properties (size, surface area, etc.) of particles and fibres and also of the suspension medium including its ionic strength, pH, and temperature. In vitro dissolution tests can provide useful insights as to how particles and fibres may react in biological environments; particles and fibres that release ions at a higher rate when suspended in vitro in a specific simulated biological fluid will be expected to do so when they exist in a similar biological environment in vivo. Dissolution of particles and fibres can follow different reaction kinetics. For example, the majority of micro-sized particles and fibres follow zero-order reaction kinetics. In this case, although it is possible to calculate the half-time of a particle or fibre, such calculation will be dependent on the initial concentration of the investigated particle or fibre. Such dependence was eliminated in the shrinking sphere and fibre models where it was possible to estimate the lifetimes of particles and fibres as a measure of their biodurability. The latter models can be adapted for the dissolution studies of nanomaterials. However, the models may apply only to nanomaterials where their dissolution follows zero-order kinetics. The dissolution of most nanomaterials follows first-order kinetics where dependence on their initial concentration of the investigated nanomaterials is not required and therefore it is possible to estimate their half-times as a measure of their biodurability. In dissolution kinetics for micro-sized and nano-sized particles and fibres, knowledge of dissolution rate constants is necessary to understand biodurability. Unfortunately, many studies on dissolution of nanoparticles and nanofibres do not determine the dissolution rates and dissolution rate constants. The recommendation is that these parameters should be considered as part of the important descriptors of particle and fibre physicochemical properties, which in turn, will enable the determination of their biodurability.

Radon exposure risks among residents proximal to gold mine tailings in Gauteng Province, South Africa: a cross-sectional preliminary study protocol.

Gold mine tailings, a legacy of the mining industry, harbors significant amount of radon gas, a classified human carcinogen. Radon exposure, especially near tailings, is a significant public health threat, potentially leading to increased risk of lung cancer, leukemia, and chronic obstructive pulmonary disease (COPD). These health problems are often associated with lower survival rates and significant financial burdens. This ongoing research aim to evaluating the relationship between indoor radon exposure and lung cancer, leukemia, and COPD risks among residents proximal to gold mine tailings in Gauteng Province, South Africa. This cross-sectional preliminary study focus on two distinct groups: Riverlea (exposed group, <2 km to Gold mine tailings) and Orlando East (unexposed group, >2 km to Gold mine tailings). Indoor radon levels is measured using AlphaE monitors, while health risks (lung cancer, leukemia, and COPD) linked to exposure are evaluated through interview-administered questionnaire and secondary data from Gauteng Health Department. Of the 476 residents randomly selected for this study, 300 have already participated, with balanced representation from both the exposed and unexposed groups. The study will compare indoor radon levels and health outcomes between the two groups. This study's results could aid in creating targeted interventions and policies to mitigate indoor radon exposure risks and safeguard vulnerable communities from this significant public health hazard.

Issues and Challenges in the Application of the IEUBK Model in the Health Risk Assessment of Lead: A Case Study from Blantyre Malawi.

The risk assessment of lead (Pb) requires the use of biokinetic models to translate measured concentrations of Pb in food and environmental media into blood lead (BPb). The aim of this study was to assess the applicability of the Integrated Exposure Uptake Biokinetic (IEUBK) model in the health risk assessment of Pb among children in Blantyre. Children (152) aged 1-6 years were recruited into this cross-sectional study, and foods, house dust, playground soil, water, and venous blood (1 mL) were collected and analyzed for Pb. A seven-day food frequency questionnaire (FFQ) was used to collect food consumption data. The concentrations of Pb ranged from 0.01 to 3.3 mg/kg in food, 2.3 to 265 mg/kg and 1.5 to 482 mg/kg in house dust and playground soil, respectively, as well as 2.0 µg/dL to 50.4 µg/dL and 6.8 to 39.2 µg/dL for measured and predicted BPb, respectively. Various statistical tests indicated less than satisfactory agreement between measured and predicted BPb values. Despite the lack of reliable food consumption data and other limitations, both the predicted and measured BPb values indicate that children in Blantyre are exposed to high levels of Pb, largely through food and soil as a minor source.

Study Protocol to Determine Association between Environmental Triggers and Asthma among Children in King Williams Town.

Asthma affects over 330 million people worldwide, with relatively higher disease burdens in Australia, New Zealand, Africa, the Middle East, and South America. The symptoms associated with asthma were reported to be prevalent in children from the period of 1993 to 2013, in many low- and middle-income countries, due to changes in environmental conditions, such as domestic lifestyle, and urban and industrial developments. (1) Background: Several studies have also shown that children are prone to a severe type of asthma, because of their narrow respiratory airways and susceptibility to irritation from environmental agents. This study aimed to assess the association between environmental exposure and asthma among children in King Williams Town, South Africa. (2) Methodology: This study adopted a cross-sectional design method, with an estimated sample size of 262 participants. The eligible study participants were enrolled while attending Grey hospital in King Williams Town, for asthma management. Information will be collected from eligible, stable participants, on asthma treatment, through in-person interviewing in 2021. A semi-structured questionnaire will be administered to the participants. However, as a result of the prevailing COVID-19 pandemic, data may be abstracted from the asthma medical record of the eligible participants. Multivariate regression will be utilized, to describe the correlation between the variables, and the odds ratio will be calculated as well. (3) Discussion and conclusion: The study will objectively identify the local environmental agents that are associated with asthma among children in King Williams Town, in order to reprioritize treatment and preventative strategies. Ethical approval was obtained from the Research Ethics Committee, Faculty of Health Sciences at the University of Johannesburg.

Gut microbiota-mediated pesticide toxicity in humans: Methodological issues and challenges in the risk assessment of pesticides.

Many in vivo and in vitro studies have shown that pesticides can disrupt the functioning of gut microbiota (GM), which can lead to many diseases in humans. While the tests developed by the Organization of Economic Cooperation and Development (OECD) are expected to capture most apical effects resulting from GM disruptions, exclusion of GM in the risk assessment might mischaracterize hazards or overestimate/underestimate risks, especially when extrapolating results from one species to another species or population with a substantially different GM. On the other hand, direct assessment of GM-mediated effects may face challenges in identifying hazards, since not all GM perturbations will lead to human adverse effects. In this regard, reliable and validated biomarkers for common GM-mediated adverse effects may be very useful in the identification of GM-mediated pesticide toxicity. Nevertheless, proving causality of GM-mediated effects will need modifications of Bradford Hill criteria as well as Koch's postulates, which are more suitable for the "one-pathogen" paradigm. Furthermore, risk assessment of GM-mediated effects may require pesticide toxicokinetics along the gut, possibly through modeling, and the establishment of the involvement of GM in the mechanism of action (MOA) of the pesticide. Risk assessment of GM mediated effects also requires the standardization of experimental approaches as well as the establishment of microbial reference communities, since variations exist among GM in human populations.

Impact of level five lockdown on the incidence of COVID-19: lessons learned from South Africa.

INTRODUCTION: the level five (L5) lockdown was a very stringent social distancing measure taken to reduce the spread of COVID-19 infections. This study assessed the impact of the L5 lockdown and its association with the incidence of COVID-19 cases in South Africa (SA). METHODS: data was obtained from the National Department of Health (NDoH) from the 5th March to the 30th April 2020. A basic reproductive number (R0) and a serial interval were used to calculate estimated cases (EC). A double exponential smoothing model was used to forecast the number of cases during the L5 lockdown period. A Poisson regression model was fitted to describe the association between L5 lockdown status and incident cases. RESULTS: a total of 5,737 laboratory-confirmed cases (LCC) were reported by 30th April 2020, 4,785 (83%) occurred during L5 lockdown. Our model forecasted 30,629 cases of COVID-19 assuming L5 lockdown was not imposed. High incidence rates of COVID-19 were recorded in KwaZulu-Natal and Mpumalanga Provinces during the L5 lockdown compared to the other provinces. Nationally, the incident rate of COVID-19 was 68.00% higher in L5 lockdown than pre-lockdown for LCC. CONCLUSION: the L5 lockdown was very effective in reducing the incidence of COVID-19 cases. However, the incident rates of LCC and EC were higher nationally, and in some provinces during the L5 lockdown.

A Critical Review of the Status of Pesticide Exposure Management in Malawi.

Pesticides pose a significant risk to humans and the environment. This paper analyzes the measures used to manage pesticides in Malawi. Malawi's regulatory authority of pesticides, the Pesticides Control Board (PCB), faces a number of challenges including lack of facilities for analyzing pesticides and inadequate personnel to conduct risk assessment of pesticides. The PCB needs to provide access to information and opportunities among the public to make contributions regarding requirements, processes and policies for assessing pesticide risk and efficacy. There is also a need to enhance the capacity of PCB to assess pesticide poisoning in workers, monitor pesticide residues in food and environmental contamination, as well as to control the illegal importation and sale of pesticides. Just like in other countries such as South Africa, India and Sri Lanka, Malawi urgently needs to implement measures that can restrict the importation, production, sale and use of very toxic pesticides. Malawi also needs to develop measures for the effective management of pesticide waste containers as well as obsolete pesticides, where potential solutions include reducing the purchase of (unneeded) pesticides, treatment of obsolete pesticides in high-temperature cement kilns, as well as requesting pesticide dealers to adopt life-cycle management of their products.

Current Approaches and Techniques in Physiologically Based Pharmacokinetic (PBPK) Modelling of Nanomaterials.

There have been efforts to develop physiologically based pharmacokinetic (PBPK) models for nanomaterials (NMs). Since NMs have quite different kinetic behaviors, the applicability of the approaches and techniques that are utilized in current PBPK models for NMs is warranted. Most PBPK models simulate a size-independent endocytosis from tissues or blood. In the lungs, dosimetry and the air-liquid interface (ALI) models have sometimes been used to estimate NM deposition and translocation into the circulatory system. In the gastrointestinal (GI) tract, kinetics data are needed for mechanistic understanding of NM behavior as well as their absorption through GI mucus and their subsequent hepatobiliary excretion into feces. Following absorption, permeability (Pt) and partition coefficients (PCs) are needed to simulate partitioning from the circulatory system into various organs. Furthermore, mechanistic modelling of organ- and species-specific NM corona formation is in its infancy. More recently, some PBPK models have included the mononuclear phagocyte system (MPS). Most notably, dissolution, a key elimination process for NMs, is only empirically added in some PBPK models. Nevertheless, despite the many challenges still present, there have been great advances in the development and application of PBPK models for hazard assessment and risk assessment of NMs.

An investigation of maternal anaemia among HIV infected pregnant women on antiretroviral treatment in Johannesburg, South Africa.

INTRODUCTION: maternal anaemia is a major public health problem in developing countries. Data suggests that anaemia contributes to the progression of Human Immunodeficiency Virus (HIV)-infection. The aim of this study was to investigate if pregnancy was an aggravating factor for anaemia among HIV-positive women on anti-retroviral treatment (ART). METHODS: we analyzed data of all HIV-positive women aged 18-49 years receiving ART at Themba Lethu Clinic, Helen Joseph Hospital, Johannesburg, South Africa, from 1st April 2004- 30t hApril 2011. HIV-positive pregnant women were matched with non-pregnant women using the year of initiation of treatment. The outcome of interest ´anaemia´ was defined as "no anaemia", "anaemia" and "moderate/severe anaemia". We fitted an ordered logistic regression model to predict the likelihood of having severe/moderate anaemia versus no anaemia. We included pregnancy status as a predictor of the outcome and controlled the effect of other covariates in the analysis. RESULTS: the study included 236 HIV positive patients, of which half (n=118, 50%) were pregnant. At baseline, about (n=143, 60%) of patients were anaemic. The proportion of pregnant women classified as anaemic (anaemia, moderate/severe) differed significantly (p=0.02) from that of non-pregnant women. The following characteristics were significantly associated with anaemia at baseline: Body mass index (BMI) category (p=0.01); World Health Organization (WHO) stage (p=0.001) and CD4 count (p=0.001). Seven months after initiation of treatment, the proportion of HIV positive women with anaemia decreased significantly. CONCLUSION: anaemia is a significant risk factor for untoward health outcomes, especially among HIV-positive pregnant women. Early ART access might result in a significant decrease in anaemia in pregnancy.

Chirality, a neglected physico-chemical property of nanomaterials? A mini-review on the occurrence and importance of chirality on their toxicity.

Toxicity assessments are required for nanomaterials which are being used in many fields such as medicines, electronics, pesticides, clothes and construction materials. One factor that usually affects toxicity of chemicals is chirality. This paper reviews the existence of chirality in nanoparticles and critically analyses the implications of chirality on toxicological risk assessment of nanoparticles. Chirality and optical activity arise from lack of symmetry, where an object is non-superimposable on its mirror image. Optical isomers or enantiomers have similar physico-chemical properties but only differ in their optical activity and their interaction with biological systems. Chirality is not limited to organic molecules, but also exists in inorganic compounds and crystals. Studies have also shown that chirality can be bestowed onto nanoparticles by adsorption of chiral molecules, and by careful design of the crystal to expose chiral kinked and stepped surface structures. Just as chirality has been shown to affect the biological activities of conventional chemicals, nanoparticles functionalised with different enantiomers have been shown to exhibit enantioselectivity and different toxicities. However, at the moment more studies on the ligands and the conditions under which chirality occurs in NPs, as well as on the effects of NP chirality on protein adsorption kinetics and thermodynamics. Nevertheless, this cursory analysis has shown the importance of chirality on biological activity of nanoparticles. In cases where there is a potential for the existence of chirality in nanomaterials (either intrinsic or extrinsic), there may be need for adequate consideration of the effects of chirality.

Exceedance of environmental exposure limits to crystalline silica in communities surrounding gold mine tailings storage facilities in South Africa.

BACKGROUND: Unlike occupational silica exposures, the association between non-occupational silica exposures and adverse health effects is not well researched, despite its occurrence in communities close to dust-generating sources such as tailings storage facilities (TSFs). Recent studies have shown that communities surrounding TSFs in South Africa often complain about the onset of dust-related health effects. Even though international interim non-occupational crystalline silica limits have been established, South Africa is yet to enforce its own limits for residential areas close to TSF sites. OBJECTIVE: The objective of the study was to assess the need to enforce non-occupational crystalline silica limits for South Africa. METHODS: The methods involved (1) Quantifying the silica polymorph content in bulk dust collected from TSFs in South Africa; (2) Assessing the possibility of the dust to reach surrounding communities through ambient and personal filter sampling and; (3) Conducting risk characterisation for both cancer and non-cancer endpoints. RESULTS: All bulk dust samples consisted mostly of crystalline silica (73.14-87.09%). Large percentages of nanoparticles were identified in all bulk samples (66.8-70.7%) indicating the possibility of the dust to lodge deep within the lungs. The crystalline silica levels obtained from ambient PM10 sampling and personal PM4 sampling all exceeded the international crystalline silica interim limits and reached maximum levels of 90 and 50.9µg·m-3, respectively. For three TSFs, sampling sites close to the TSFs showed higher PM4 silica levels compared to sites further from TSFs. Risk characterisation revealed the possibility of cancer and non-cancer health effects when chronically exposed to silica levels recorded during the study. CONCLUSION: The results indicate unacceptable crystalline silica exposures in surrounding communities and the need for enforcement of an ambient silica limit for South Africa.

An assessment of applicability of existing approaches to predicting the bioaccumulation of conventional substances in nanomaterials.

The experimental determination of bioaccumulation is challenging, and a number of approaches have been developed for its prediction. It is important to assess the applicability of these predictive approaches to nanomaterials (NMs), which have been shown to bioaccumulate. The octanol/water partition coefficient (KOW ) may not be applicable to some NMs that are not found in either the octanol or water phases but rather are found at the interface. Thus the KOW values obtained for certain NMs are shown not to correlate well with the experimentally determined bioaccumulation. Implementation of quantitative structure-activity relationships (QSARs) for NMs is also challenging because the bioaccumulation of NMs depends on nano-specific properties such as shape, size, and surface area. Thus there is a need to develop new QSAR models based on these new nanodescriptors; current efforts appear to focus on digital processing of NM images as well as the conversion of surface chemistry parameters into adsorption indices. Water solubility can be used as a screening tool for the exclusion of NMs with short half-lives. Adaptation of fugacity/aquivalence models, which include physicochemical properties, may give some insights into the bioaccumulation potential of NMs, especially with the addition of a biota component. The use of kinetic models, including physiologically based pharmacokinetic models, appears to be the most suitable approach for predicting bioaccumulation of NMs. Furthermore, because bioaccumulation of NMs depends on a number of biotic and abiotic factors, it is important to take these factors into account when one is modeling bioaccumulation and interpreting bioaccumulation results. Environ Toxicol Chem 2018;37:2972-2988. © 2018 SETAC.

Sharing perspectives and experiences of doctoral fellows in the first cohort of Consortium for Advanced Research Training in Africa: 2011-2014.

BACKGROUND: Resolution of public health problems in Africa remains a challenge because of insufficient skilled human resource capacity. The Consortium for Advanced Research Training in Africa (CARTA) was established to enhance capacity in multi-disciplinary health research that will make a positive impact on population health in Africa. OBJECTIVE: The first cohort of the CARTA program describes their perspectives and experiences during the 4 years of fellowship and puts forward suggestions for future progress and direction of research in Africa. CONCLUSIONS: The model of training as shown by the CARTA program is an effective model of research capacity building in African academic institutions. An expansion of the program is therefore warranted to reach out to more African academics in search of advanced research training.